Valero, Julian and Civit, Laia and Dupont, Daniel M. and Selnihhin, Denis and Reinert, Line S. and Idorn, Manja and Israels, Brett A. and Bednarz, Aleksandra M. and Bus, Claus and Asbach, Benedikt and Peterhoff, David and Pedersen, Finn S. and Birkedal, Victoria and Wagner, Ralf and Paludan, Soren R. and Kjems, Jorgen (2021) A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 118 (50): e211294211. ISSN 0027-8424, 1091-6490
Full text not available from this repository. (Request a copy)Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an urgent need for new technologies to treat COVID-19. Here we report a 20-fluoro protected RNA aptamer that binds with high affinity to the receptor binding domain (RBD) of SARS-CoV-2 spike protein, thereby preventing its interaction with the host receptor ACE2. A trimerized version of the RNA aptamer matching the three RBDs in each spike complex enhances binding affinity down to the low picomolar range. Binding mode and specificity for the aptamer-spike interaction is supported by biolayer interferometry, single-molecule fluorescence microscopy, and flow-induced dispersion analysis in vitro. Cell culture experiments using virus-like particles and live SARS-CoV-2 show that the aptamer and, to a larger extent, the trimeric aptamer can efficiently block viral infection at low concentration. Finally, the aptamer maintains its high binding affinity to spike from other circulating SARS-CoV-2 strains, suggesting that it could find wide-spread use for the detection and treatment of SARS-CoV-2 and emerging variants.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECEPTOR-BINDING DOMAIN; NANOBODIES; SPIKE; ANTIBODIES; MUTATIONS; PROTEIN; aptamer selection; SARS-CoV-2 targeting; aptamer multimerization; viral neutralization; spike protein |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Sep 2022 13:00 |
| Last Modified: | 12 Sep 2022 13:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47214 |
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